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Studies on The Expression of Genes during Lung Development and Differentiation

肺发育分化过程中基因表达的研究

基本信息

批准号：
02404040
负责人：
YAMAGUCHI Etsuro
金额：
$ 20.74万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (A)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1993
项目状态：
已结题

项目摘要

We analyzed abnormalities of p53 gene of prifmary lung cancer tissues, using a immunohistochemical method and PCR-SSCP.Abnormal p53 genes were observed in a high frequency for squamous cell carcinoma and small cell carcinoma, and in a low frequency for adenocarcinoma. The frequency of the abnormalities was higher in smokers than in nonsmokers, suggesting p53 is the target gene in the development of lung cancer in smokers. The abnormalities were significantly associated with the poor prognosis in cure resection cases.Collagen vascular diseases (CVD) have been thought to be involved in the etiology of idiopathic interstitial pneumonia (IIP). Silica particles were directly instilled into the trachea of 1pr/1pr mice which develop CVD spontaneously and +/+ mice as the control strain. Fibrosis was unexpectedly weaker in 1pr/1pr than +/+. We next examined fibrogenic effects of bleomycin and silica in ozone-sensitive C57/B16J mice and ozone-insensitive C3H/HeJ mice. Though fibrosis in the acute phase was strong in C57/B16J when bleomycin was injected, it was similar when silica was instilled, suggesting the fibrotic process induced by bleomycin is different from that induced by silica.TNF alpha is a potent granulomatogenic cytokine released from monocyte-macrophage lineage cells. We studied the ability of LPS-stimulated alveolar macrophages to release TNFalpha, and found significantly increased production in sarcoid patients compared with healthy subjects. We also detected GM-CSF mRNA expressed by bronchoalveolar lavage cells in sarcoid patients by the sensitive RT-PCR method. Its expression was significantly associated with a protracted clinical course and the presence of extra-pulmonary lesions. These results further strengthened the important roles of the cytokine network in the formation and maintenance of sarcoid granulomas.

我们采用免疫组化和PCR-SSCP方法分析原发性肺癌组织中p53基因的异常。p53基因异常在鳞状细胞癌和小细胞癌中频率较高，在腺癌中频率较低。吸烟者中出现这种异常的频率高于非吸烟者，这表明p53是吸烟者肺癌发展的靶基因。这些异常与治愈切除病例的不良预后显著相关。胶原血管病（CVD）被认为与特发性间质性肺炎（IIP）的病因有关。将二氧化硅颗粒直接灌注到自发发生CVD的1pr/1pr小鼠和对照株+/+小鼠的气管中。1pr/1pr组的纤维化出乎意料地弱于+/+。接下来，我们研究了博来霉素和二氧化硅对臭氧敏感的C57/B16J小鼠和臭氧不敏感的C3H/HeJ小鼠的纤维化作用。虽然注射博来霉素时C57/B16J急性期纤维化较强，但灌注二氧化硅时则相似，说明博来霉素诱导的纤维化过程与二氧化硅诱导的纤维化过程不同。TNF α是从单核-巨噬细胞谱系细胞释放的一种有效的致肉芽肿细胞因子。我们研究了lps刺激的肺泡巨噬细胞释放TNFalpha的能力，发现与健康受试者相比，肉瘤患者的巨噬细胞释放TNFalpha的能力显著增加。我们还采用灵敏的RT-PCR方法检测了肉瘤患者支气管肺泡灌洗细胞表达的GM-CSF mRNA。它的表达与延长的临床病程和肺外病变的存在显著相关。这些结果进一步强化了细胞因子网络在肉芽肿形成和维持中的重要作用。